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维生素A可减轻全氟辛烷磺酸诱导的斑马鱼幼体神经毒性,并改变其与同种个体的早期接近模式。

Vitamin A attenuates PFOS-induced neurotoxicity and alters early proximity patterns to conspecifics in zebrafish larvae.

作者信息

Jiang Peiyun, Wang Jingyu, Wang Xiaoying, Zou Li, Wu Di, Xu Qu, Jiang Yue, Yao Mengmeng, Hong Qin, Chi Xia

机构信息

Women's Hospital of Nanjing Medical University (Nanjing Women and Children's Healthcare Hospital), Nanjing, China.

Department of Pediatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

出版信息

Front Behav Neurosci. 2025 Jun 5;19:1564694. doi: 10.3389/fnbeh.2025.1564694. eCollection 2025.

Abstract

INTRODUCTION

Perfluorooctane sulfonic acid (PFOS), a persistent perfluoroalkyl substance with ubiquitous environmental distribution and bioaccumulative potential, has raised significant public health concerns due to its association with neurodevelopmental disorders. This study investigates vitamin A's neuroprotective capacity against PFOS-induced toxicity, particularly focusing on social behavior deficits-a core phenotype of autism spectrum disorder (ASD).

METHODS

Zebrafish larvae were exposed to 1 μM or 5 μM PFOS (with/without 5 nM vitamin A co-treatment) from 24-144 hours post-fertilization (hpf). Control groups received 0.01% DMSO (vehicle) or 5 nM vitamin A alone. Developmental parameters (body length, heart rate), locomotor activity (total distance moved), and neurobehavioral endpoints (conspecific interaction) were quantified using automated tracking systems (ViewPoint ZebraLab). Neurochemical alterations were assessed through qPCR (dopaminergic genes) and AO staining (apoptosis).

RESULTS

PFOS exposure (5 μM) significantly increased inter-individual distance (IID) and reduced physical contact frequency during social interaction tests. Neurochemical analyses revealed concurrent dopamine transporter downregulation and apoptosis-related gene activation . Vitamin A co-treatment attenuated these effects.

DISCUSSION

Our findings demonstrate that PFOS disrupts early social neurodevelopment through dopaminergic dysregulation and apoptotic signaling, while vitamin A exhibits counteractive potential. this study elucidates the impact of PFOS exposure on zebrafish social behavior and brain development. while highlighting the neuroprotective potential of vitamin A against PFOS exposure, These findings have significant guiding implications for the development of public health policy and provide a scientific foundation for comprehending the neurotoxicity of PFOS and developing effective intervention measures.

摘要

引言

全氟辛烷磺酸(PFOS)是一种持久性全氟烷基物质,在环境中广泛分布且具有生物累积潜力,因其与神经发育障碍有关,已引起公众对其重大健康问题的关注。本研究调查了维生素A对PFOS诱导毒性的神经保护能力,特别关注社交行为缺陷——自闭症谱系障碍(ASD)的核心表型。

方法

将斑马鱼幼体在受精后24至144小时(hpf)暴露于1μM或5μM的PFOS(有/无5 nM维生素A联合处理)。对照组分别接受0.01%二甲基亚砜(溶剂)或单独的5 nM维生素A。使用自动跟踪系统(ViewPoint ZebraLab)对发育参数(体长、心率)、运动活性(移动的总距离)和神经行为终点(同种相互作用)进行量化。通过qPCR(多巴胺能基因)和AO染色(凋亡)评估神经化学变化。

结果

PFOS暴露(5μM)在社交互动测试中显著增加个体间距离(IID)并降低身体接触频率。神经化学分析显示多巴胺转运体同时下调和凋亡相关基因激活。维生素A联合处理减轻了这些影响。

讨论

我们的研究结果表明,PFOS通过多巴胺能失调和凋亡信号传导破坏早期社交神经发育,而维生素A具有对抗潜力。本研究阐明了PFOS暴露对斑马鱼社交行为和大脑发育的影响。在强调维生素A对PFOS暴露的神经保护潜力的同时,这些发现对公共卫生政策的制定具有重要指导意义,并为理解PFOS的神经毒性和制定有效干预措施提供了科学依据。

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